A commentary on “Models of Consent to Return of Incidental Findings in Genomic Research,” by Paul S. Appelbaum, Erik Parens, Cameron R. Waldman, Robert Klitzman, Abby Fyer, Josue Martinez, W. Nicholson Price II, and Wendy K. Chung, in the July‐August 2014 issue.

Temporal discounting is a technical operation in climate change economics. When discount rates are positive, economic evaluation treats future benefits as less important than equivalent present benefits. This chapter explains and critically evaluates four different reasons economists have given for tying discount rates to the interest rates we observe in real-world markets. I suggest that while philosophers have correctly criticized three of these reasons, their criticisms of the fourth miss the mark. This is because philosophers have not taken heed of (...) the distinct analytical framework in which the fourth reason arises. (shrink)

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

Several areas of welfare economics seek to evaluate states of affairs as a function of interpersonally comparable individual utilities. The aim is to map each state of affairs onto a vector of individual utilities, and then to produce an ordering of these vectors that can be represented by a mathematical function assigning a real number to each. When this approach is used in intertemporal contexts, a central theoretical question concerns the evaluative weight to be applied to utility coming at different (...) times. This question concerns the rate of pure time preference, which is one key determinant of the social discount rate. This article argues that the standard philosophical account of pure time preference is mistaken, because it ascribes to economists a methodological commitment they need not, and often do not, accept. This in turn undercuts the most common philosophical objection to pure time preference, which traces at least to Rawls’s A Theory of Justice. The article then evaluates three further objections to pure time preference, concluding that it might still be defensible under certain circumstances. The article closes by articulating a final argument that is suggested by the “Social, Economic and Ethical Concepts and Methods” chapter of the most recent Intergovernmental Panel on Climate Change report. If this further argument is sound, it would constitute a decisive objection to pure time preference as it currently figures in much intertemporal welfare economics. (shrink)

Although Alston believed epistemically circular arguments were able to justify their conclusions, he was also disquieted by them. We will argue that Alston was right to be disquieted. We explain Alston’s view of epistemic circularity, the considerations that led him to accept it, and the purposes he thought epistemically circular arguments could serve. We then build on some of Alston’s remarks and introduce further limits to the usefulness of such arguments and introduce a new problem that stems from those limits. (...) The upshot is that adopting Alston’s view that epistemically circular arguments can be used to justify their conclusions is more costly than even he thought. (shrink)

Generating an account that can sidestep the disagreement among substantive theories of well-being, while at the same time still providing useful guidance for well-being public policy, would be a significant achievement. Unfortunately, the various attempts to remain agnostic regarding what constitutes well-being fail to either be an account of well-being, provide useful guidance for well-being policy, or avoid relying on a substantive well-being theory. There are no theory-free lunches in well-being policy. Instead, I propose an intermediate account, according to which (...) well-being is constituted by endorsed veridical experiences. This account refers back to theories of well-being but does so as agnostically as possible. An intermediate account of well-being is meant as a policy guiding compromise between the different theories of well-being that make claims regarding what constitutes well-being. An intermediate account does as well as can be hoped for in providing a basis for well-being policy. (shrink)

It is an open question whether well-being ought to primarily be understood as a temporal concept or whether it only makes sense to talk about a person’s well-being over their whole lifetime. In this article, I argue that how this principled philosophical disagreement is settled does not have substantive practical implications for well-being science and well-being policy. Trying to measure lifetime well-being directly is extremely challenging as well as unhelpful for guiding well-being public policy, while temporal well-being is both an (...) adequate indirect measure of lifetime well-being, and an adequate focus for the purposes of improving well-being through public policy. Consequently, even if what we ought to care about is lifetime well-being, we should use temporal measures of well-being and focus on temporal well-being policies. (shrink)

Policy-makers sometimes aim to improve well-being as a policy goal, but to do this they need some way to measure well-being. Instead of relying on potentially problematic theories of well-being to justify their choice of well-being measure, Daniel Hausman proposes that policy-makers can sometimes rely on preference-based measures as evidence for well-being. I claim that Hausman’s evidential account does not justify the use of any one measure more than it justifies the use of any other measure. This leaves us at (...) a loss as to which policy should be chosen in the non-trivial cases for which there is substantial disagreement between the different measures in their assessment of policy. (shrink)

For Rawls, the demands of justice compete with moral and religious obligations that are part of citizens’ comprehensive doctrines. The ways we love are shaped by our comprehensive doctrines; however, love can also stand in opposition to our moral and religious beliefs. I will argue that love – spousal, familial and associational – constitutes its own register of values along with its own set of obligations. For this reason love confronts not only our moral and religious beliefs, it also confronts (...) the demands and requirements of justice. Rawls has worked out a negotiated peace between the obligations of justice and the demands of citizens’ comprehensive doctrines in the form of an overlapping consensus on a free-standing political conception of justice. I will argue that in Rawls’s philosophy, justice has not yet made peace with love. (shrink)

Many philosophers reject the view that well-being over a lifetime is simply an aggregation of well-being at every moment of one's life, and thus they reject theories of well-being like hedonism and concurrentist desire satisfactionism. They raise concerns that such a view misses the importance of the relationships between moments in a person's life or the role narratives play in a person's well-being. In this article, we develop an atomist meta-theory of well-being, according to which the prudential value of a (...) life depends solely on the prudential value of each moment of that life. This is a general account of momentary well-being that can capture different features of well-being that standard atomistic accounts fail to capture, thus allowing for the possibility of an atomism that is compatible with a variety of well-being theories. Contrary to many criticisms leveled against momentary well-being, this well-being atomism captures all of the important features of well-being. (shrink)

Alasdair MacIntyre argues that moral virtues are antithetical to what is required of those who trade in financial markets to succeed. MacIntyre focuses on four virtues and argues that successful traders possess none of them: (i) self-knowledge, (ii) courage, (iii) taking a long-term perspective, and (iv) tying one’s own good with some set of common goods. By contrast, I argue that (i)–(iii) are, in fact, traits of successful traders, regardless of their normative assessment. The last trait – caring about the (...) common good – is often counterproductive in most for-profit ventures, including trading, and so singling out traders is inappropriate. (shrink)

Philosophers of well-being have tended to adopt a foundationalist approach to the question of theory and measurement, according to which theories are conceptually before measures. By contrast, social scientists have tended to adopt operationalist commitments, according to which they develop and refine well-being measures independently of any philosophical foundation. Unfortunately, neither approach helps us overcome the problem of coordinating between how we characterize well-being and how we measure it. Instead, we should adopt a coherentist approach to well-being science.

Many believe that an upward-sloping life is better than a downward-sloping life because of its shape. This is a common way of formulating the shape of a life hypothesis. We argue that the hypothesis is mistaken. We need not assume that there is something intrinsically valuable in the shape of one’s life to justify the tendency to judge an upward-sloping life as better than a downward sloping one. Instead, we can appeal to more fundamental and less controversial claims to justify (...) such a judgment. What one might justifiably judge to be better are features of lives which are often (though not necessarily) correlated with, rather than constituted by, an upward slope. (shrink)

Is there a principled way to understand what liberal democratic states owe, as a matter of justice, to the victims of disasters? This article shows what is normatively special and distinctive about disasters and argues for the view that there are substantial duties of justice for liberal democratic states. The article rejects both a libertarian and a utilitarian approach to this question and, based on broadly Rawlsian principles, argues for a ‘political definition’ of disasters that is concerned with the restoration (...) of citizens' dignity and their capacities for effective citizenship. (shrink)

In order to fight massive vandalism the English- language Wikipedia has developed a system of surveillance which is carried out by humans and bots, supported by various tools. Central to the selection of edits for inspection is the process of using filters or profiles. Can this profiling be justified? On the basis of a careful reading of Frederick Schauer’s books about rules in general (1991) and profiling in particular (2003) I arrive at several conclusions. The effectiveness, efficiency, and risk-aversion of (...) edit selection all greatly increase as a result. The argument for increasing predictability suggests making all details of profiling manifestly public. Also, a wider distribution of the more sophisticated anti-vandalism tools seems indicated. As to the specific dimensions used in profiling, several critical remarks are developed. When patrollers use ‘assisted edit- ing’ tools, severe ‘overuse’ of several features (anonymity, warned before) is a definite possibility, undermining profile efficacy. The easy remedy suggested is to render all of them invisible on the interfaces as displayed to patrollers. Finally, concerning not only assisted editing tools but tools against vandalism generally, it is argued that the anonymity feature is a sensitive category: anons have been in dispute for a long time (while being more prone to vandalism). Targeting them as a special category violates the social contract upon which Wikipedia is based. The feature is therefore a candidate for mandatory ‘underuse’: it should be banned from all anti-vandalism filters and profiling algorithms, and no longer be visible as a special edit trait. (shrink)

How should we make distributive decisions when there is not enough of the good to go around, or at least not enough of it right now? What does fairness require in such cases? In what follows, we distinguish between cases of scarcity and bottleneck cases, and we argue that both arguments for lotteries and arguments for queues have merit, albeit for different distributive scenarios. When dealing with scarcity not everyone can get the good. A secondary good that can be distributed (...) fairly is the chances of obtaining the good. In cases of scarcity, lotteries are the best way of allocating chances of obtaining the good fairly. When dealing with bottlenecks, the secondary good that can and ought to be distributed fairly is waiting time. Queues are best suited to distribute the good of waiting time fairly. (shrink)

Spoofing is the act of placing orders to buy or sell a financial contract without the intention to have those orders fulfilled in order to create the impression that there is a large demand for that contract at that price. In this article, I deny the view that spoofing in financial markets should be viewed as morally permissible analogously to the way bluffing is permissible in poker. I argue for the pro tanto moral impermissibility of spoofing and make the case (...) that spoofing is disanalogous from bluffing in at least one important regard—speculative trading serves an important economic role, whereas poker does not. (shrink)

The move from open outcry to electronic trading added another responsibility to futures exchanges—that of matching orders between buyers and sellers. Matching systems can affect the level and speed of price discovery, the distribution of revenue, as well as the level of price efficiency of a given market. Whether the matching system is procedurally fair is another important consideration. I argue that while FIFO (First In First Out) is a fair procedure in principle and is perceived as the default matching (...) system, it is not a fair procedure in practice. Likewise, while pro rata is a fair procedure in principle, it is not so in practice. Nevertheless, both FIFO and pro rata are relics of an open outcry system. Instead, I propose an alternative approach to matching systems that builds on the strengths of electronic trading—the ability to randomize in real time. I introduce random selection for service (RSS) as a matching system that is procedurally fair both in principle and in practice. (shrink)

According to what I call the ‘argument from public bads’, if a researcher deceived subjects in the past, there is a chance that subjects will discount the information that a subsequent researcher provides, thus compromising the validity of the subsequent researcher’s experiment. While this argument is taken to justify an existing informal ban on explicit deception in experimental economics, it can also apply to implicit deception, yet implicit deception is not banned and is sometimes used in experimental economics. Thus, experimental (...) economists are being inconsistent when they appeal to the argument from public bads to justify banning explicit deception but not implicit deception. (shrink)

In this paper we discuss James Buchanan’s contribution in the narrow domain of understanding committee voting under majority rule. We then go on to discuss Charles Plott’s seminal experimental work on the topic that sparked a wave of public choice experimental work. However, given Plott’s claims that Buchanan influenced him significantly, it is puzzling that his work with Morris Fiorina explores a question outside of those which Buchanan and Tullock found interesting. We suggest several ways to resolve this tension. Our (...) chapter concludes by discussing a lacuna in the experimental public choice literature in which Buchanan was particularly interested—logrolling, or vote trading. (shrink)

In book II of Plato’s Republic, Socrates discusses the cities of necessity and luxury (372d-373a). Discussions of these cities have often focused on citizens desiring more than they need, which creates a demand for luxury. Yet the second part of the equation, which is not usually recognized, is that there must be sufficient supply to meet this demand. The focus of this article is on the importance of supply in the discussion of the first two cities in book II of (...) the Republic. This article argues that the way Plato models the cities makes it the case that a surplus above levels of necessity will be generated from time to time. That the unwanted surplus cannot be spontaneously disposed of entails that the first two cities are institutionally incomplete. A government is needed in order to coordinate the disposal of the surplus supply the city will produce. (shrink)

Abstract: Introspection reveals that one is frequently conscious of some form of inner speech, which may appear either in a condensed or expanded form. It has been claimed that this speech reflects the way in which language is involved in conscious thought, fulfilling a number of cognitive functions. We criticize three theories that address this issue: Bermúdez’s view of language as a generator of second-order thoughts, Prinz’s development of Jackendoff’s intermediate-level theory of consciousness, and Carruthers’s theory of inner speech as (...) a rehearsal of action-schemata. We contend they have problems to account for those cases in which inner speech is fragmentary, and for the difference with those instances in which it appears as more sentence-like. In addition, we present verbal overshadowing as a phenomenon that neither of them can easily explain. Finally, we propose an account in which inner speech is fundamentally silent outer speech and argue that it is more explanatory than the alternatives. (shrink)

This paper addresses the relationship between logic and phenomenology at a historical moment that precedes the big divide between analytic philosophy and phenomenology. In analysing alternative derivations of phenomenological logic, the discussion focuses on the case of two notorious neo-Kantian Mexican philosophers from the first half of the XXth century: Adalberto García de Mendoza and Francisco Larroyo. It is argued that both García de Mendoza and Larroyo made an original contribution to the discussion on the relationship between phenomenology and logic. (...) Further, this paper attempts to present a charitable portrait of both García de Mendoza and Larroyo in contrast to underrating approaches to both Mexican philosophers. In so doing, this paper adopts a historical—though not strictly biographical— perspective. While it is true that neither García de Mendoza nor Larroyo could be considered “phenomenologists” or “Husserl scholars” according to contemporary standards it is worth noticing that they engage in the discussion of phenomenological logic. Both authors had the project of developing a grounding logic for science and, as the article argues, both attempts could be even linked. Their project, however, was unfinished. The plan of this paper is as follows. The first section addresses the problem of the relationship between logic and phenomenology. The second one focuses on García de Mendoza’s contributions. The third one elaborates on Larroyo’s Logic of Sciences. And, finally, the fourth section elaborates on these Mexican philosophers’ contributions to education, making as well further observations concerning the similarities and differences between both authors. (shrink)

A widespread Western conception about the sanctity of the human body and its parts prevents from any morally acceptable disposition of these objects. However, this entails nothing but a dualistic conception of the human being as a composite of detachable parts — namely, body and mind. Understood as the antechamber of legal rights, moral rights perform an important — yet frequently overlooked — justifying function that permeates the political discourse. Although the connection among moral, political and legal discourses should be (...) properly acknowledged, certain boundaries are to mediate among each scope for the sake of certainty and accuracy. Intermediate realities, as the so-called human rights, serve to connect the moral and legal domains, still they also blur the lines along which the discourse is deployed. Moral entities are essentially inalienable, to the extent that they demarcate the moral status of the subject. By contrast, legal rights are essentially negotiable and, thus, alienable. The controversial instance of bodily rights will serve to test the assertions above. (shrink)

Intentionalism is the view that perceptual phenomenology depends on perceptual content. The aim of this paper is to make explicit an ambiguity in usual formulations of intentionalism, and to argue in favor of one way to disambiguate it. It concerns whether perceptual phenomenology depends on the content of one and only one representation (often construed as being identical to a certain perceptual experience), or instead depends on a collection of many different representations throughout the perceptual system. We argue in favor (...) of the latter option. Intentionalism so conceived can make better sense of contemporary neuroscience of perception, and is better equipped to confront several influential objections to traditional intentionalism. (shrink)

We present a dynamic model of the evolution of communication in a Lewis signaling game while systematically varying the degree of common interest between sender and receiver. We show that the level of common interest between sender and receiver is strongly predictive of the amount of information transferred between them. We also discuss a set of rare but interesting cases in which common interest is almost entirely absent, yet substantial information transfer persists in a *cheap talk* regime, and offer a (...) diagnosis of how this may arise. -/- . (shrink)

I explore some of the connections between Grahek's model of asymbolic pain, as developed in Feeling Pain and Being in Pain, and the contemporary intentionalist discussion over evaluativist and imperativist models of pain. I will sketch a Grahekian version of imperativism that is both true to his main insights and better at confronting some of the challenges that his theory has faced since its publication.

There has been much discussion of so-called teleosemantic approaches to the naturalization of content. Such discussion, though, has been largely confined to simple, innate mental states with contents such as ?There is a fly here.? Even assuming we can solve the issues that crop up at this stage, an account of the content of human mental states will not get too far without an account of productivity: the ability to entertain indefinitely many thoughts. The best-known teleosemantic theory, Millikan's biosemantics, offers (...) an account of productivity in thought. This paper raises a basic worry about this account: that the use of mapping functions in the theory is unacceptable from a naturalistic point of view. (shrink)

Descartes holds that when you perceive something with perfect clarity, you are compelled to assent and cannot doubt. (This is a psychological claim.) Many commentators read him as endorsing Psychologism, according to which this compulsion is a matter of brute psychological force. I show that, in Descartes’s view, perfect clarity provides a reason for assent—indeed a perfect reason, which precludes any reason for doubt. (This is a normative claim.) Furthermore, advancing a view I call Rational Force, he holds that the (...) normative claim explains the psychological one: since your will is naturally responsive to reasons, you are compelled to assent because you have a perfect reason to assent. This coheres with his view that will is essentially active, self-determined, and free. The force that clarity exerts on the will is not the brute push of an efficient cause, but the rational pull of a final cause. (shrink)

There is a dimension of rationality, known as structural rationality, according to which a paradigmatic example of what it means to be rational is not to be akratic. Although some philosophers claim that aesthetics falls within the scope of rationality, a non-akrasia constraint prohibiting certain combinations of attitudes is yet to be developed in this domain. This essay is concerned with the question of whether such a requirement is plausible and, if so, whether it is an actual requirement of aesthetic (...) rationality. Ultimately, this paper defends the view that aesthetics is no different from other domains in that it requires coherence between a subject’s mental states (in the aesthetic case, between what is judged and what is aesthetically liked). (shrink)

We explore the contribution made by oscillatory, synchronous neural activity to representation in the brain. We closely examine six prominent examples of brain function in which neural oscillations play a central role, and identify two levels of involvement that these oscillations take in the emergence of representations: enabling (when oscillations help to establish a communication channel between sender and receiver, or are causally involved in triggering a representation) and properly representational (when oscillations are a constitutive part of the representation). We (...) show that even an idealized informational sender–receiver account of representation makes the representational status of oscillations a non-trivial matter, which depends on rather minute empirical details. (shrink)

Linguistics of saying studies language in its birth. Language is the mental activity executed by speaking subjects. Linguistics of saying consists in analyzing speech acts as the result of an act of knowing. Speaking subjects speak because they have something to say. Tthey say because they define themselves before the circumstance they are in. And this is possible because they are able to know. Speaking, then, is speaking, saying and knowing. In this sense there is a progressive determination. Knowing makes (...) possible saying, and saying determines speaking, or, in other words: speaking involves saying and knowing, and saying involves knowing. The problem thus is to determine the meaningful intentional purpose of the individual speaker to say something in every speech act. (shrink)

Both Franz Brentano and Edmund Husserl addressed sound while trying to explain the inner consciousness of time and gave to it the status of a supporting example. Although their inquiries were not aimed at clarifying in detail the nature of the auditory experience or sounds themselves, they made some interesting observations that can contribute to the current philosophical discussion on sounds. On the other hand, in analytic philosophy, while inquiring the nature of sounds, their location, auditory experience or the audible (...) qualities and so on, the representatives of that trend of thought have remained silent about the depiction of sound and the auditory phenomena in the phenomenological tradition. The paper’s intention is to relate both endeavours, yet the perspective carried out is that of analytic philosophy and, thus, I pay special attention to conceptual analysis as a methodological framework. In this sense, I first explain what sound ontology is in the context of analytic philosophy and the views that it encompasses— namely, the Property View (PV), the Wave View (WV) and the Event View (EV)—. Secondly, I address the problems it entails, emphasising that of sound individuation. In a third section, I propose the possibly controversial conjunction of a “Brentano-Husserl Analysis of the Consciousness of Time” (for short “Brentano-Husserl analysis”) and outline the commonalities of both authors, without ignoring its discrepancies. My main focus is Husserl’s 1905 Vorlesungen zur Phänomenologie des Inneren Zeitbewusstseins. While addressing the Brentano-Husserl analysis, I elaborate on the problem of temporal and spatial extension (Raumlichkeit and Zeitlichkeit, respectively) of both consciousness and sound. Such comparison is a key one, since after these two developments, one can notice some theoretical movements concerning the shift of attention from sounds to the unity of consciousness, and how they mirror each other. After examining the controversial claims concerning the temporal and spatial extension of both consciousness and sound, I argue in the concluding paragraphs that while considering the accounts of sound ontology, the Brentano-Husserl analysis would probably endorse a Property View and that this could have interesting consequences for the issue of Sound Individuation. (shrink)

It is widely held that it is unhelpful to model our epistemic access to modal facts on the basis of perception, and postulate the existence of a bodily mechanism attuned to modal features of the world. In this paper I defend modalizing mechanisms. I present and discuss a decision-theoretic model in which agents with severely limited cognitive abilities, at the end of an evolutionary process, have states which encode substantial information about the probabilities with which the outcomes of a certain (...) Bernoulli process occur. Thus, in the model, a process driven by very simple, thoroughly naturalistic mechanisms eventuates in modal sensitivity. (shrink)

El autor del artículo edita y estudia una inscripción funeraria inédita de época helenística encontrada en Aptera (Creta) por la arqueóloga griega V. Ninioú-Kindelí. El texto de la inscripción dice así: A) Σώσανδρος | Βίτωνος. B) Ἀμφιμήδης | Σωσάνδρω.

I respond to an objection recently formulated by Barlassina and Hayward against first-order imperativism about pain, according to which it cannot account for the self-directed motivational force of pain. I am going to agree with them: it cannot. This is because pain does not have self-directed motivational force. I will argue that the alternative view—that pain is about dealing with extramental, bodily threats, not about dealing with itself—makes better sense of introspection, and of empirical research on pain avoidance. Also, a (...) naturalistic theory of body-involving commands falls straightforwardly out of our most prominent naturalistic metasemantic accounts, while the token-reflexive contents that would underlie self-directed motivation are more problematic. (shrink)

Why do we have social norms—of fairness, cooperation, trust, property, or gender? Modern-day Humeans, as I call them, believe these norms are best accounted for in cultural evolutionary terms, as adaptive solutions to recurrent problems of social interaction. In this paper, I discuss a challenge to this “Humean Program.” Social norms involve widespread behaviors, but also distinctive psychological attitudes and dispositions. According to the challenge, Humean accounts of norms leave their psychological side unexplained. They explain, say, why we share equally, (...) but not why we disapprove of those who don’t. I defend the Humean Program against this challenge. In particular, I suggest an idea for how to extend the Program to account for the psychological side of norms. Socially adaptive behaviors aren’t just likely to emerge in a group; They are also likely to be widely taught within it. The transmission of these behaviors through instruction explains why they are associated with distinctive normative attitudes and dispositions. These attitudes play a pedagogical role in helping transmit these behaviors to children and newcomers. (shrink)

Language is nothing but human subjects in as much as they speak, say and know. Language is something coming from the inside of the speaking subject manifest in the intentional meaningful purpose of the individual speaker. A language, on the contrary, is something coming from the outside, from the speech community, something offered to the speaking subject from the tradition in the technique of speaking. The speech act is the performance of an intuition by the subject, both individual and social.

La filosofía de la ciencia se desarrolló durante la primera mitad del siglo xx bajo el supuesto de que la ciencia podía caracterizarse por la estructura lógica tanto del conocimiento articulado en las teorías más exitosas como de sus explicaciones. En la segunda mitad del siglo xx se cuestiona fuertemente esa idea, pero se sigue asumiendo que la filosofía de la ciencia debe hacerse siguiendo los cánones de una epistemología fundamentalista que considera que el avance de la ciencia pasa por (...) una ontología cada vez mas austera guiada por la idea de "mientras menos mejor". Desde esta perspectiva fundamentalista, el que las diferentes ciencias hablen de diferentes tipos de cosas es un obstáculo al entendimiento, producto de la imperfección del conocimiento actual. Este ideal nos invita a pensar que la epistemología debe hacerse reflexionando sobre el conocimiento articulado en nuestras teorías más austeras y nos compromete con propuestas reduccionistas problemáticas que no permiten explicar la diversidad de recursos epistémicos que de hecho utilizan los científicos. En este libro promovemos una epistemología que no sigue el lema de "mientras menos mejor", sino el de "organizar nuestros recursos epistémicos de manera que se genere entendimiento". Así, la misma estructura de las explicaciones y las prácticas (que incluye métodos y normas respecto de lo que se considera plausible y valioso) es lo que nos da la pauta para responder a la pregunta de qué es lo que hay. Esta estrategia epistémica nos obliga a hacer una filosofía de la ciencia muy cercana a la ciencia, reconociendo la pluralidad de sus métodos, objetivos y prácticas, sin reducir la filosofía de la ciencia a la sociología o a cualquier otra ciencia en particular. (shrink)

Recent work on signaling has mostly focused on communication between organisms. The Lewis–Skyrms framework should be equally applicable to intra-organismic signaling. We present a Lewis–Skyrms signaling-game model of painful signaling, and use it to argue that the content of pain is predominantly imperative. We address several objections to the account, concluding that our model gives a productive framework within which to consider internal signaling.

The human subject in as much as he knows transforms the sensitive and concrete (the thing perceived) into abstract (an image of the thing perceived), the abstract into an idea (imaginative representation of the thing abstracted), and ideas into contents of conscience (meanings). The last step in the creation of meanings, something being executed in the speech act, consists in fixing the construct mentally created thus making it objectified meanings in the conscience of speakers. The interchange amongst the different steps (...) in the creation of meaning manifests lógos, the state lived by speakers in their interior when speaking, created and developed in words and because of words. (shrink)

The concept of autonomy is central to many debates in aesthetics. However, exactly what it means to be autonomous in our aesthetic engagements is somewhat unclear in the philosophical literature. The normative significance of autonomy is also unclear and hotly debated. In this essay, I propose a method for clarifying this elusive concept by distinguishing three distinct senses or varieties of aesthetic autonomy: experiential autonomy, competence-based autonomy, and personal autonomy. On this taxonomy autonomy is a context-sensitive concept and autonomy applies (...) to several different moments or stages of aesthetic appreciation. Throughout this critical discussion, important issues concerning the nature of aesthetic appreciation are also explored. (shrink)

Philosophical discussions on cognition (ranging from computational and representational approaches to the 4E fra-mework), on the one hand, and those on sound and auditory per-ception, on the other, have hitherto remained apart. In this paper, the author addresses the concept of “auditory cognition”. While committing to the conceptual analysis of the latter, the author in-troduces the discussion of modality-specif ic approaches. Since the contributions made so far in the domain of the philosophy of sound and auditory perception are prone to (...) favor computational-repre-sentational approaches —e.g., the perceptual coherence model (Méndez-Martínez, 2022)—, the exploration of 4E possibilities will lay down a series of questions aimed to encourage future developers from that viewpoint. In that sense, the author explores conceptual entailments and connections between the genealogy of theories within the philosophy of sound and auditory perception, and the hypothesis of the extended cognition (EX). (shrink)

Introduction: Traditionally, empathy has been studied from two main perspectives: the theory-theory approach and the simulation theory approach. These theories claim that social emotions are fundamentally constituted by mind states in the brain. In contrast, classical phenomenology and recent research based on enactive theories consider empathy as the basic process of contacting others’ emotional experiences through direct bodily perception and sensation. Objective: This study aims to enrich knowledge of the empathic experience of pain by using an experimental phenomenological method. Method: (...) Implementing an experimental paradigm used in affective neuroscience, we exposed 28 healthy adults to a video of sportspersons suffering physical accidents while practicing extreme sports. Immediately after watching the video, each participant underwent a phenomenological interview to gather data on embodied, multi-layered dimensions (bodily sensations, emotions, and motivations) and temporal aspects of empathic experience. We also performed quantitative analyses of the phenomenological categories. Results: Experiential access to the other person’s painful experience involves four main-themes. Bodily resonance: participants felt a multiplicity of bodily, affective, and kinesthetic sensations. Attentional focus: some participants centered their attention more on their own personal discomfort and sensations of rejection, while others on the pain and suffering experienced by the sportspersons. Kinesthetic motivation: some participants experienced the feeling in their bodies to avoid or escape from watching the video, while others experienced the need to help the sportspersons avoid suffering any injury while practicing extreme sports. Temporality of experience: participants witnessed temporal fluctuations in their experiences, bringing intensity changes in their bodily resonance, attentional focus, and kinesthetic motivation. Finally, two experiential structures were found: one structure is self-centered empathic experience, characterized by bodily resonance, attentional focus centered on the participant’s own experience of seeing the sportsperson suffering, and self-protective kinesthetic motivation; the other structure is other-centered empathic experience, characterized by bodily resonance, attentional focus centered on the sportsperson, and prosocial kinesthetic motivation to help them. Discussion: We show how phenomenological data may contribute to comprehending empathy for pain in social neuroscience. In addition, we address the phenomenological aspect of the enactive approach to the three dimensions of embodiment of human consciousness, especially the intersubjective dimension. Also, based on our results, we suggest an extension of the enactive theory for non-interactive social experience. (shrink)

(This is one of the essays to be included in a book examining the causes of day-to-day strife in the populations of modern democracies vying to live and assert the freedoms promised to them by systems of governance supposed and expected to represent them.) -/- The emigrant / immigrant / migrant makes a conscious, relatively difficult decision to exchange what s/he knows for what is not known at all but in promise. The choice is often stark and carries with it (...) the imposition of restrictions on what will be possible in terms of existing customs, culture, and direct involvement with friends and family, and signifies a leap of faith into what appears to be a better, more prosperous, happier future. -/- At times, such choice is unavoidable, others it turns out to be a gamble of sorts, but, no matter what the cause, reason, or desire underlying an act of migration away from what the emigrant has known, it never turns out to be what was expected and no amount of preparation allows the emigrant to anticipate what will in fact occur. Migration is the founding of a new life in all the aspects of the emigrant’s existence. (shrink)

This essay focuses on theories of creativity from six historical figures, while noting comparisons to several others. In Ancient Greece: (i) Plato advances the thesis that the poet is a passive vessel inspired by a muse. (ii) Aristotle replies with the antithesis that the poet creates through skilled activity. (iii) Longinus provides the synthesis. Plato is right that poets are passively inspired with original ideas – though the source is natural genius instead of some muse. But Aristotle is also right (...) that the poet must actively employ skill. In early modern Europe: (iv) Margaret Cavendish argues that through creativity women can enjoy some freedom and happiness despite oppression. (v) Alexander Gerard and Immanuel Kant both inherit the Longinian synthesis. Gerard says we form original ideas through remote associations. (vi) Kant notices that although the genius must be passive in the origination of ideas, she must also be active in the very same process, because she merits acclaim for her originality. Kant designs his theory of genius to resolve this Paradox of Creative Agency. (shrink)

This paper does three interrelated things. First, it argues that the universalism that forms the target of criticism and attack by decolonial theorists from the Global South is a debased form of universalism, what might be termed “ethnocentric universalism.” Second, equipped with a conceptual grip on ethnocentric universalism, it shows that the picture on which ethnocentric universalism confers some innocuous epistemic privilege to members of dominant groups is not quite accurate—ethnocentric universalism is incompatible with the epistemic flourishing of members of (...) dominant groups. And third, based on that claim, and the additional consideration that ethnocentric universalism equally undermines the epistemic flourishing of members of historically marginalized groups, it proposes an emancipatory framework for engaging with it. (shrink)

in recent years, policy makers have shown increasing interest in implementing policies aimed at promoting individual well-being. But how should policy makers choose their well-being policies? a seemingly reasonable first step is to settle on an agreed-upon definition of well-being. yet there currently is significant disagreement on how well-being ought to be characterized, and agreement on the correct view of well-being does not appear to be forthcoming. Nevertheless, i argue in this paper that there are several reasons to think that (...) the domain of well-being in the public policy context is narrower than that of well-being in general, which makes agreement on how to understand well-being in the public policy context more likely. (shrink)